K-252a is an indolocarbazole whose stereochemistry is shown below (Formula I): ##STR2##
K-252a inhibits protein kinase C (PKC), which plays a role in regulating cell functions. K-252a has various activities, e.g., inhibiting smooth muscle contraction (Jap. J. Pharmacol. 43 (suppl.): 284, 1987), inhibiting serotonin secretion (Biochem. Biophys. Res. Commun. 144: 35, 1987), inhibiting elongation of neuraxone (J. Neurosci. 8:715, 1988), inhibiting histamine release (Allergy 43:100, 1988), inhibiting smooth muscle MLCK (J. Biol. Chem. 263:6215, 1988), anti-inflammatory action (Acta Physiol. Hung. 80:423, 1992), and promotion of cell survival (J. Neurochem. 64:1502, 1995). K-252a also inhibits IL-2 production (Exper. Cell Res. 193:175-182, 1991). The total synthesis of the natural (+) isomer of K252a and its enantiomeric (-) isomer (all three chiral carbons of the sugar moiety inverted), has been achieved (Wood et al., J. Am. Chem. Soc. 117:10413, 1995; and WO 97/07081).